Discharge Disposition and Loss of Independence Among Survivors of COVID-19 Admitted to Intensive Care: Results From the SCCM Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS).

OBJECTIVES: To describe incidence and risk factors of loss of previous independent living through nonhome discharge or discharge home with health assistance in survivors of intensive care unit (ICU) admission for coronavirus disease 2019 (COVID-19). DESIGN: Multicenter observational study including patients admitted to the ICU from January 2020 till June 30, 2021. HYPOTHESIS: We hypothesized that there is a high risk of nonhome discharge in patients surviving ICU admission due to COVID-19. SETTING: Data were included from 306 hospitals in 28 countries participating in the SCCM Discovery Viral Infection and Respiratory Illness Universal Study COVID-19 registry. PATIENTS: Previously independently living adult ICU survivors of COVID-19. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was nonhome discharge. Secondary outcome was the requirement of health assistance among patients who were discharged home. Out of 10 820 patients, 7101 (66%) were discharged alive; 3791 (53%) of these survivors lost their previous independent living status, out of those 2071 (29%) through nonhome discharge, and 1720 (24%) through discharge home requiring health assistance. In adjusted analyses, loss of independence on discharge among survivors was predicted by patient age ≥ 65 years (adjusted odds ratio [aOR] 2.78, 95% confidence interval [CI] 2.47-3.14, P < .0001), former and current smoking status (aOR 1.25, 95% CI 1.08-1.46, P = .003 and 1.60 (95% CI 1.18-2.16), P = .003, respectively), substance use disorder (aOR 1.52, 95% CI 1.12-2.06, P = .007), requirement for mechanical ventilation (aOR 4.17, 95% CI 3.69-4.71, P < .0001), prone positioning (aOR 1.19, 95% CI 1.03-1.38, P = .02), and requirement for extracorporeal membrane oxygenation (aOR 2.28, 95% CI 1.55-3.34, P < .0001). CONCLUSIONS: More than half of ICU survivors hospitalized for COVID-19 are unable to return to independent living status, thereby imposing a significant secondary strain on health care systems worldwide.

Association of hypothyroidism with outcomes in hospitalized adults with COVID-19: Results from the International SCCM Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS): COVID-19 Registry.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) is associated with high rates of morbidity and mortality. Primary hypothyroidism is a common comorbid condition, but little is known about its association with COVID-19 severity and outcomes. This study aims to identify the frequency of hypothyroidism in hospitalized patients with COVID-19 as well as describe the differences in outcomes between patients with and without pre-existing hypothyroidism using an observational, multinational registry. METHODS: In an observational cohort study we enrolled patients 18 years or older, with laboratory-confirmed severe acute respiratory syndrome coronavirus-2 infection between March 2020 and February 2021. The primary outcomes were (1) the disease severity defined as per the World Health Organization Scale for Clinical Improvement, which is an ordinal outcome corresponding with the highest severity level recorded during a patient's index COVID-19 hospitalization, (2) in-hospital mortality and (3) hospital-free days. Secondary outcomes were the rate of intensive care unit (ICU) admission and ICU mortality. RESULTS: Among the 20,366 adult patients included in the study, pre-existing hypothyroidism was identified in 1616 (7.9%). The median age for the Hypothyroidism group was 70 (interquartile range: 59-80) years, and 65% were female and 67% were White. The most common comorbidities were hypertension (68%), diabetes (42%), dyslipidemia (37%) and obesity (28%). After adjusting for age, body mass index, sex, admission date in the quarter year since March 2020, race, smoking history and other comorbid conditions (coronary artery disease, hypertension, diabetes and dyslipidemia), pre-existing hypothyroidism was not associated with higher odds of severe disease using the World Health Organization disease severity index (odds ratio [OR]: 1.02; 95% confidence interval [CI]: 0.92, 1.13; p = .69), in-hospital mortality (OR: 1.03; 95% CI: 0.92, 1.15; p = .58) or differences in hospital-free days (estimated difference 0.01 days; 95% CI: -0.45, 0.47; p = .97). Pre-existing hypothyroidism was not associated with ICU admission or ICU mortality in unadjusted as well as in adjusted analysis. CONCLUSIONS: In an international registry, hypothyroidism was identified in around 1 of every 12 adult hospitalized patients with COVID-19. Pre-existing hypothyroidism in hospitalized patients with COVID-19 was not associated with higher disease severity or increased risk of mortality or ICU admissions. However, more research on the possible effects of COVID-19 on the thyroid gland and its function is needed in the future.

A systematic review and meta-analysis of glycemic control for the prevention of diabetic foot syndrome.

OBJECTIVE: The objective of this review was to synthesize the available randomized controlled trials (RCTs) estimating the relative efficacy and safety of intensive vs less intensive glycemic control in preventing diabetic foot syndrome. METHODS: We used the umbrella design (systematic review of systematic reviews) to identify eligible RCTs. Two reviewers determined RCT eligibility and extracted descriptive, methodologic, and diabetic foot outcome data. Random-effects meta-analysis was used to pool outcome data across studies, and the I(2) statistic was used to quantify heterogeneity. RESULTS: Nine RCTs enrolling 10,897 patients with type 2 diabetes were included and deemed to be at moderate risk of bias. Compared with less intensive glycemic control, intensive control (hemoglobin A1c, 6%-7.5%) was associated with a significant decrease in risk of amputation (relative risk [RR], 0.65; 95% confidence interval [CI], 0.45-0.94; I(2) = 0%). Intensive control was significantly associated with slower decline in sensory vibration threshold (mean difference, -8.27; 95% CI, -9.75 to -6.79). There was no effect on other neuropathic changes (RR, 0.89; 95% CI, 0.75-1.05; I(2) = 32%) or ischemic changes (RR, 0.92; 95% CI, 0.67-1.26; I(2) = 0%). The quality of evidence is likely moderate. CONCLUSIONS: Compared with less intensive glycemic control therapy, intensive control may decrease the risk of amputation in patients with diabetic foot syndrome. The reported risk reduction is likely overestimated because the trials were open and the decision to proceed with amputation could be influenced by glycemic control.

A systematic review and meta-analysis of débridement methods for chronic diabetic foot ulcers.

BACKGROUND: Several methods of débridement of diabetic foot ulcers are currently used. The relative efficacy of these methods is not well established. METHODS: This systematic review and meta-analysis was conducted to find the best available evidence for the effect of débridement on diabetic foot wound outcomes. We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus through October 2011 for randomized controlled studies (RCTs) and observational comparative studies. RESULTS: We identified 11 RCTs and three nonrandomized studies reporting on 800 patients. The risk of bias was moderate overall. Meta-analysis of three RCTs showed that autolytic débridement significantly increased the healing rate (relative risk [RR], 1.89; 95% confidence interval [CI] 1.35-2.64). Meta-analysis of four studies (one RCT) showed that larval débridement reduced amputation (RR, 0.43; 95% CI, 0.21-0.88) but did not increase complete healing (RR, 1.27; 95% CI, 0.84-1.91). Surgical débridement was associated with shorter healing time compared with conventional wound care (one RCT). Insufficient evidence was found for comparisons between autolytic and larval débridement (one RCT), between ultrasound-guided and surgical débridement, and between hydrosurgical and surgical débridement. CONCLUSIONS: The available literature supports the efficacy of several débridement methods, including surgical, autolytic, and larval débridement. Comparative effectiveness evidence between these methods and supportive evidence for other methods is of low quality due to methodologic limitations and imprecision. Hence, the choice of débridement method at the present time should be based on the available expertise, patient preferences, the clinical context and cost.

A systematic review and meta-analysis of adjunctive therapies in diabetic foot ulcers.

BACKGROUND: Multiple adjunctive therapies have been proposed to accelerate wound healing in patients with diabetes and foot ulcers. The aim of this systematic review is to summarize the best available evidence supporting the use of hyperbaric oxygen therapy (HBOT), arterial pump devices, and pharmacologic agents (pentoxifylline, cilostazol, and iloprost) in this setting. METHODS: We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus through October 2011. Pairs of independent reviewers selected studies and extracted data. Predefined outcomes of interest were complete wound healing and amputation. RESULTS: We identified 18 interventional studies; of which 9 were randomized, enrolling 1526 patients. The risk of bias in the included studies was moderate. In multiple randomized trials, the addition of HBOT to conventional therapy (wound care and offloading) was associated with increased healing rate (Peto odds ratio, 14.25; 95% confidence interval, 7.08-28.68) and reduced major amputation rate (odds ratio, 0.30; 95% confidence interval, 0.10-0.89), compared with conventional therapy alone. In one small trial, arterial pump devices had a favorable effect on complete healing compared with HBOT and in another small trial compared with placebo devices. Neither iloprost nor pentoxifylline had a significant effect on amputation rate compared with conventional therapy. No comparative studies were identified for cilostazol in diabetic foot ulcers. CONCLUSIONS: There is low- to moderate-quality evidence supporting the use of HBOT as an adjunctive therapy to enhance diabetic foot ulcer healing and potentially prevent amputation. However, there are only sparse data regarding the efficacy of arterial pump devices and pharmacologic interventions.

A systematic review and meta-analysis of off-loading methods for diabetic foot ulcers.

BACKGROUND: Increased plantar foot pressure is one of several key factors that lead to diabetic foot ulcers. Multiple methods have been proposed to relieve this pressure and thus enhance wound healing and potentially prevent relapse. We aimed in this systematic review to find the best available evidence for off-loading methods. METHODS: We searched MEDLINE, Embase, Cochrane CENTRAL, Web of Science, and Scopus through October 2011. Pairs of independent reviewers selected studies and extracted data. Predefined outcomes of interest included complete wound healing, time to complete wound healing, amputation, infection, and relapse rates. RESULTS: We identified 19 interventional studies, of which 13 were randomized controlled trials, including data from 1605 patients with diabetic foot ulcers using an off-loading method. The risk of bias in the included studies was moderate. This analysis demonstrated improved wound healing with total contact casting over removable cast walker, therapeutic shoes, and conventional therapy. There was no advantage of irremovable cast walkers over total contact casting. There was improved healing with half-shoe compared with conventional wound care. Therapeutic shoes and insoles reduced relapse rate in comparison with regular footwear. Data were sparse regarding other off-loading methods. CONCLUSIONS: Although based on low-quality evidence (ie, evidence warranting lower certainty), benefits are demonstrated for use of total contact casting and irremovable cast walkers in the treatment of diabetic foot ulcers. Reduced relapse rate is demonstrated with various therapeutic shoes and insoles in comparison with regular footwear.

Adverse effects of the common treatments for polycystic ovary syndrome: a systematic review and meta-analysis.

CONTEXT: Polycystic ovary syndrome (PCOS) is common among women of childbearing age and the available pharmacological therapies have different side-effect profiles. OBJECTIVE: We summarized the evidence about the side effects of oral contraceptive pills, metformin, and anti-androgens in women with PCOS. DATA SOURCE: Sources included Ovid Medline, OVID EMBASE, OVID Cochrane Library, Web of Science, Scopus, PsycInfo, and CINAHL from inception through April 2011. STUDY SELECTION: We included comparative observational studies enrolling women with PCOS who received the agents of choice for at least 6 months and reported adverse effects. DATA EXTRACTION: Using a standardized, piloted, and Web-based data extraction form and working in duplicate, we abstracted data from each study and performed meta-analysis when possible. DATA SYNTHESIS: We found 22 eligible studies of which 20 were randomized. No study reported severe side effects (eg, lactic acidosis, thromboembolic episodes, liver toxicity, cancer incidence, or pregnancy loss). Meta-analysis demonstrated no significant change in weight in oral contraceptive pills or flutamide users. Indirect evidence from populations without PCOS demonstrated no increased risk of lactic acidosis with metformin, only case reports of liver toxicity with flutamide (no comparative evidence), and increased relative risk difference of venous thromboembolism with oral contraceptive pills but very low absolute risk. Evidence on mortality, cardiovascular mortality, and cancer was inconclusive. CONCLUSIONS: Drugs commonly used to treat PCOS appear to be associated with very low risk of severe adverse effects although data are extrapolated from other populations.

Lifestyle modification programs in polycystic ovary syndrome: systematic review and meta-analysis.

CONTEXT: Polycystic ovary syndrome (PCOS) is a prevalent disorder that affects women of childbearing age and may be related to obesity and insulin resistance. OBJECTIVE: The purpose of this systematic review was to appraise the evidence of the impact of lifestyle modification (LSM) interventions on outcomes of women with PCOS. DATA SOURCES: Sources included Ovid Medline, OVID Embase, OVID Cochrane Library, Web of Science, Scopus, PsycINFO, and CINAHL (up to January 2011). STUDY SELECTION: We included randomized controlled trials that enrolled woman of any age with PCOS who received LSM and compared them against women who received no intervention, minimal intervention, or metformin. DATA EXTRACTION: Two authors performed the data extraction independently. DATA SYNTHESIS: We included 9 trials enrolling 583 women with a high loss to follow-up rate, lack of blinding, and short follow-up. Compared with minimal intervention, LSM significantly reduced fasting blood glucose (weighted mean difference, -2.3 mg/dL; 95% confidence interval, -4.5 to -0.1, I² = 72%, P = .04) and fasting blood insulin (weighted mean difference, -2.1 µU/mL, 95% confidence interval, -3.3 to -1.0, I² = 0%, P < .001). Changes in body mass index were associated with changes in fasting blood glucose (P < .001). Metformin was not significantly better than LSM in improving blood glucose or insulin levels. We found no significant effect of LSM on pregnancy rate, and the effect on hirsutism was unclear. CONCLUSIONS: The available evidence suggests that LSM reduces fasting blood glucose and insulin levels in women with PCOS. Metformin has similar effects. Translation of these short-term effects to patient-important outcomes, beyond diabetes prevention, remains uncertain.

Screening for gestational diabetes: a systematic review and meta-analysis.

CONTEXT: Gestational diabetes mellitus (GDM) is defined as any degree of hyperglycemia with first recognition during pregnancy. The optimal time to screen for GDM that would maximize the yield and benefits remains unclear. OBJECTIVE: Our objective was to appraise the evidence regarding screening for GDM (accuracy, correlation with adverse outcomes, and harms). DATA SOURCES: We searched Ovid Medline, OVID EMBASE, OVID Cochrane Library, Web of Science, Scopus, PsycInfo, and CINAHL through May 2011. STUDY SELECTION: We included randomized controlled trials and observational studies that enrolled pregnant woman who were evaluated using different GDM screening tests. DATA EXTRACTION: Two reviewers working independently abstracted the data. RESULTS: We did not find any randomized controlled trials of GDM screening that measured feto-maternal outcomes. A 1-hour 50-g glucose challenge test with a cutoff point at 140 mg/dL was the most commonly used screening method. The results of this test were statistically associated with feto-maternal outcomes (P < .001), even though only 11% of individuals with a positive test (according to Carpenter and Coustan criteria) developed GDM. Positive Carpenter and Coustan criteria were associated with macrosomia (odds ratio [OR] = 2.4, 95% confidence interval [CI] = 1.9-3.1, P < .001) and gestational hypertension (OR = 1.7, CI = 1.3-2.1, P < .001). Positive National Diabetes Data Group criteria were also associated with macrosomia (OR = 3.2, CI = 2.3-4.4, P < .001) and gestational hypertension (OR = 2.1, CI = 1.6-2.8, P < .001). CONCLUSIONS: Indirect evidence supports the use of contemporary screening tests for GDM to identify pregnancies at increased risk of adverse feto-maternal outcomes. It also suggests that use of these tests will place some women under unnecessary treatment for GDM.

Treatment outcomes of human bartonellosis: a systematic review and meta-analysis.

BACKGROUND: Bartonella henselae, Bartonella quintana, and Bartonella bacilliformis are responsible for the majority of cases of bartonellosis in humans. These species have various unique epidemiologic characteristics, clinical manifestations, and treatment approaches. The objective of this study was to summarize the evidence on the treatment for the three most common species of Bartonella in humans. METHODS: We searched electronic databases through August 2011 for randomized controlled trials and observational studies designed to evaluate the efficacy and safety of the regimens used to treat diseases produced by B. henselae, B. quintana, and B. bacilliformis. Study selection and appraisal were done in duplicate. RESULTS: We found two randomized and seven non-randomized studies at high risk of bias. For cat scratch disease, antibiotics did not significantly affect the cure rate or time to achieve cure. In chronic bacteremia, gentamicin and doxycycline significantly increased the resolution rate. The recommended treatment was not better than other regimens for infectious endocarditis and bacillary angiomatosis. CONCLUSIONS: Current clinical practice for the treatment of bartonellosis relies mostly on expert opinion and antimicrobial susceptibility data. Randomized controlled trials are needed in the field to compare different treatment options.

Precisión de la taquipnea y las retracciones subcostales como signos clínicos para diagnóstico de neumonía adquirida en la comunidad en niños: revisión sistemática y metaanálisis / Identification of tachypnea and subcostal retractions as clinical signs for the diagnosis of community-acquired pneumonia among children: systematic review and meta-analysis

Objetivos. Evaluar si la taquipnea y las retracciones subcostales son predictoras eficientes para el diagnóstico de neumonía adquirida en la comunidad (NAC) en niños. Materiales y métodos. Se revisaron las bases de datos: PubMed, LILACS, The African Journal Database y The Cochrane Central Library. Se incluyeron estudios originales que evaluaron el rendimiento diagnóstico de los criterios clínicos de taquipnea o retracciones subcostales, definidos según los criterios de la Organización Mundial de la Salud (OMS) para el diagnóstico de NAC en niños de hasta cinco años de edad con tos y fiebre. Se estimaron las razones de probabilidades (LR), el odds ratio diagnostico (DOR) y sus respectivos intervalos de confianza al 95% (IC95%) para cada prueba clínica evaluada. Resultados. Se encontraron 975 estudios, incluyendo ocho en la revisión. Se enrolaron 4740 pacientes y analizaron 3584 (75%), de los cuales 916 (19%) tuvieron el diagnóstico de NAC. Al combinar los datos, la taquipnea obtuvo una LR positiva de 3,16, (IC95% 2,11-4,73) y una LR negativa de 0,36 (IC95% 0,23-0,57). El DOR fue de 10,63 (IC95% 4,4-25,66, I2=93%). Al realizar el análisis para retracciones subcostales se obtuvo un LR positivo de 2,49 (IC95% 1,41-4,37) y un LR negativo de 0,59 (IC95% 0,4-0,87). El DOR fue de 5,32 (IC95% 1,88-15,05, I2=89%). Conclusiones. Se puede tomar en cuenta la presencia o ausencia de taquipnea y retracciones subcostales en el diagnóstico de NAC, cabe considerar la incertidumbre relativa en su poder diagnóstico y los LR relativamente modestos. La confianza en estos resultados es baja por la inadecuada calidad de la evidencia en este tema.

Objectives. Determine whether tachypnea and subcostal retractions can be efficient predictors for the diagnosis of Community-Acquired Pneumonia (CAP) among children. Materials and methods. These were the databases used: PubMed, LILACS, The African Journal Database and The Cochrane Central Library. Original studies were included which assessed the diagnostic performance of the clinical criteria for tachypnea or subcostal retraction defined in accordance with the criteria of the World Health Organization (OMS) for CAP diagnosis in children ≤ 5 with cough and fever. The likelihood ratio (LR), the diagnosis odds ratio (DOR), and their respective confidence intervals at 95% (IC95%) were estimated for each clinical test. Results. 975 studies were found, eight were included in the review. 4740 patients were enrolled and 3584 (75%) were analyzed, 916 (19%) of which had a CAP diagnosis. When data were combined, tachypnea had a positive LR of 3.16, (95% CI 2.11-4.73) and a negative LR of 0.36 (95% CI 0.23-0.57). The DOR was 10.63 (95% CI 4.4-25.66, I2=93%). When subcostal retractions were analyzed, a positive LR of 2.49 (95%CI 1.41-4.37) and a negative LR of 0.59 (95%CI 0.4-0.87) were obtained. The DOR was 5.32 (95%CI 1.88-15.05, I2=89%). Conclusions. The presence or absence of tachypnea and subcostal retractions can be used in CAP diagnosis; it is worth considering the relative uncertainty in its diagnostic power and relatively modest LR. The confidence of these results is low due to the inadequate quality of the related evidence.

Body composition and quality of life in adults treated with GH therapy: a systematic review and meta-analysis.

OBJECTIVE: To summarise the evidence about the efficacy and safety of using GH in adults with GH deficiency focusing on quality of life and body composition. DATA SOURCES: We searched MEDLINE, EMBASE, Cochrane CENTRAL, Web of Science and Scopus through April 2011. We also reviewed reference lists and contacted experts to identify candidate studies. STUDY SELECTION: Reviewers, working independently and in duplicate, selected randomised controlled trials (RCTs) that compared GH to placebo. DATA SYNTHESIS: We pooled the relative risk (RR) and weighted mean difference (WMD) by the random effects model and assessed heterogeneity using the I(2) statistic. RESULTS: Fifty-four RCTs were included enrolling over 3400 patients. The quality of the included trials was fair. GH use was associated with statistically significant reduction in weight (WMD, 95% confidence interval (95% CI): -2.31 kg, -2.66 and -1.96) and body fat content (WMD, 95% CI: -2.56 kg, -2.97 and -2.16); increase in lean body mass (WMD, 95% CI: 1.38, 1.10 and 1.65), the risk of oedema (RR, 95% CI: 6.07, 4.34 and 8.48) and joint stiffness (RR, 95% CI: 4.17, 1.4 and 12.38); without significant changes in body mass index, bone mineral density or other adverse effects. Quality of life measures improved in 11 of the 16 trials although meta-analysis was not feasible. RESULTS: GH therapy in adults with confirmed GH deficiency reduces weight and body fat, increases lean body mass and increases oedema and joint stiffness. Most trials demonstrated improvement in quality of life measures.